This project examines the function of the salivary glands and other oral tissues in individuals with alterations of normal oral function due to disease or therapeutic procedures. Entry into all studies is through the Dry Mouth Clinic. Utilizing outpatient and inpatient services, specific evaluative and diagnostic approaches establish the cause and extent of salivary gland dysfunction in the "dry mouth" patient. The focus of clinical studies for many years has been primary Sj[unreadable]gren's syndrome, a systemic autoimmune exocrinopathy with major manifestations of chronic, progressive salivary and lacrimal gland dysfunction. Also studied is irradiation-induced salivary gland dysfunction associated with treatment for head and neck cancer. Oral and secretory effects of other selected systemic diseases also are evaluated. A therapeutic protocol has been completed evaluating the effectiveness of the combination of the anti- inflammatory drug hydroxychloroquine and the parasympathomimetic secretogogue pilocarpine HCL for treatment of salivary, lacrimal, and serological disease in primary Sj[unreadable]gren's syndrome patients. New studies have been initiated examining the therapeutic efficacy of thalidomide and dehydroepiandrosterone (DHEA) in primary Sjogren's syndrome. Clinical research studies are i) seeking better salivary and serologic markers of exocrine disease activity in this disorder; ii) defining the expression of cytokines and other immune mediators in the salivary glands of Sjogren's syndrome patients and normal controls; and iii) evaluating disease progression over time. Laboratory studies focus on the immunopathological mechanisms of exocrine dysfunction found in Sjogren's syndrome. Recent work has demonstrated increased expression of Fas and Fas ligand, molecules associated with apoptosis, and the inflammatory cytokine IFN-gamma, in the salivary tissues of patients with Sjogren's syndrome.